第十七章抗肿瘤药antineoplastic-agents.pptVIP

31 Decomposition of chloroethylnitrosoureas. ClCH 2 CH 2 N NO C NHR O ClCH 2 CH 2 N N OH C NR O + ClCH 2 CH 2 + + N 2 + OH - carbamoylation alkylation 氨甲酰化 32 Streptozotocin ( 链左托星 ): R=CH 3 Chlorozotocin (DCNU, 氯脲霉素 ): R=CH 2 CH 2 Cl CH 2 OH O OH OH HNHCONR OH NO 33 5. Triazemylimidazole （三氮烯咪唑类） *Dacarbazine (DTIC, 达卡巴嗪 ) 5-(3,3-dimethyl-1-triazemyl)-imidazole-4-carboxamide 临床用于黑色素病，何杰金氏病的治疗 N N N N N CH 3 CH 3 CONH 2 H 34 Bioactivation of dacarbazine. N N NH 2 CONH 2 H N N NH N N CH 3 CONH 2 H N N N N N H CH 3 CONH 2 H N N N N N CH 3 CH 3 CONH 2 H N N N N N CH 2 OH CH 3 CONH 2 H + HCHO CO 2 + OH - , N N + CH 3 or CH 2 N 2 N 2 + CH 3 + H + 肝氧化酶系 非酶水解 35 6. Hydrazine derivatives （肼类） *Procarbazine Hydrochloride ( 丙卡巴肼，甲基苄肼 ) N-isopropyl- α -(2-methyl-hydrazino-p-toluamide hydrochloride) CNHCH CH 3 NHNHCH 2 CH 3 CH 3 O . HCl 36 Bioactivation of Procarbazine hydrochloride in vivo. 烷基化 烷化 H 2 O . HCl CNHCH CH 3 NHNHCH 2 CH 3 CH 3 O CNHCH NCH 2 CH 3 CH 3 O CH 3 N CNHCH NCH 2 CH 3 CH 3 O CH 3 N O CNHCH NCH 2 CH 3 CH 3 O HOCH 2 N O -H 2 O CH 3 N + N H 2 O CNHCH N + CH 2 CH 3 CH 3 O N NADPH , O 2 NADP - NADP - , NADPH , O 2 H 2 O P-450 P-450 细胞色素 细胞色素 CNHCH NCH CH 3 CH 3 O CH 3 N O OH CNHCH NCH 2 CH 3 CH 3 O CH 3 N O 肝微粒体 肝微粒体 烷化 烷基化 p479 37 II Platinum Complex ( 金属铂配合物 ) *Cisplatin ( 顺铂 ) Cisplatin is the most active single agent against nonseminomatous( 非精原细胞瘤的 ) testicular cancer, and combinated with vinblastine and bleomycin, it is usually curative. It is also the most active single agent against ovarian cancer. Other application include treatment of squamous and transitional cell carcinomas, and treatment of small-cell lung cancer. Pt H 3 N H 3 N Cl Cl 38 III Bleomycin ( 博来霉素类 ) Bleomycin is a group of glycopeptides, with antitumor activity, isolated from Streptomyces verticillus （放线菌） . The clinical prepration is a mixture of bleomycin A 2 , A 2 I, B 1-4 , etc, with A 2 the predominant component. Bleomycin causes strand scission and fragment of DNA